High throughput Electrophysiological Purification Array (HEPA) for cell based the

用于基于细胞的高通量电生理净化阵列 (HEPA)

基本信息

批准号：
8525080
负责人：
John Collins
金额：
$ 24.96万
依托单位：
BIOPICO
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-21 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8525080
关键词：
Address Adverse effects Algorithms Amplifiers Asses Biological Assay California Cardiac Myocytes Cell Separation Cell Therapy Cells Cellular Morphology Clinical Clinical Laboratory Techniques Computer software Databases Derivation procedure Detection Development Differentiation Antigens Disease Electric Stimulation Electrodes Feasibility Studies Fluorescence-Activated Cell Sorting Fluorescent Dyes Foundations Gene Expression Genetic Glass Goals Health Heart Diseases Height Hematological Disease Human In Vitro Individual Label Laboratories Lead Lung diseases Magnetism Manuals Measurement Mechanics Methods Metric Microfluidics Microscope Modification Morphologic artifacts Myocardial Infarction Natural regeneration Noise Patients Performance Phase Phenotype Protocols documentation Pump Regenerative Medicine Replacement Therapy Response to stimulus physiology Risk Sampling Signal Transduction Somatic Cell Sorting - Cell Movement Specificity Speed Stem cells Sterility Stimulus Syringes System Techniques Technology Teratoma Therapeutic Time Tissues Transgenes Translating Translations Undifferentiated Universities Validation Ventricular Width abstracting base clinical application computerized data processing design drug development electric impedance epigenetic marker fluorexon human disease induced pluripotent stem cell novel pluripotency prevent progenitor prototype public health relevance regenerative remyelination repaired research study response sensor simulation stem cell biology stem cell differentiation tool tumor verification and validation

项目摘要

DESCRIPTION (provided by applicant): High throughput Electrophysiological Purification Array (HEPA) for cell based therapies Abstract: Patient-specific reprogrammed somatic cells (induced pluripotent stem cells or iPSCs) have raised hope for revolutionary regenerative treatments for heart, lung and blood diseases and drug development applications. For example, these iPS cells can be differentiated into cardiomyocytes and have the capability to regenerate and undergo extensive repair after myocardial infarction. However, the differentiation efficiency is low and differentiated cardiomyocytes are heterogeneous, containing mainly ventricular cardiomyocytes with varying maturation states. Since these iPSCs differentiate in vitro into a mixture of different lineages, purification of the differentiated cells, as well as their separatio from tumor-forming progenitors, is essential. But establishment of effective separation methods to isolate differentiated cells and exclude cells that lead to teratoma formation is the major challenge in translating advances in stem cell biology into tissue replacement therapies. Conventional separation techniques, such as microscope-assisted manual isolation is time consuming whereas fluorescence-activated cell sorting, and magnetic-activated cell sorting, require intensive labor, exogenous labeling or genetic modification and, as such, are not readily adaptable to clinical applications. To address these issues, therefore, Biopico Systems teams with the University of California, Irvine to develop High throughput Electrophysiological Purification Array (HEPA) system for label-free cell sorting of induced pluripotent stem cells and their differentiated progeny based on their response to electrical stimulation. This Phase I effort will provide the foundation for deriving patient specific cells for potential clinical use in phaseII with a goal of obtaining 100% specificity at high viability, high throughput and a capacity to sort multiple cell phenotypes for therapeutic applications. In order to demonstrate the feasibility of the proposed platform, we will combine the technologies of flow- based field potential sensing in an electrode array with high speed signal processing and high throughput cell sorting to rapidly detect, identify, and sort millions of specific cells that will allow the successful translation of advances in stem cell biology into therapies for cardiac diseases.

描述（由申请人提供）：用于基于细胞的疗法的高吞吐量电生理纯化阵列（HEPA）摘要：患者特定的重编程的体细胞（诱导多能干细胞或IPSC）对革命性的重新再生治疗对心脏，肺和血液疾病和血液疾病和药物发育应用的希望提高了希望。例如，这些IPS细胞可以分化为心肌细胞，并具有在心肌梗塞后再生和进行广泛修复的能力。然而，分化效率低，分化的心肌细胞是异质的，主要含有不同成熟态的心室心肌细胞。由于这些IPSC在体外分化为不同谱系的混合物，因此分化细胞的纯化以及它们与形成肿瘤的祖细胞的分离是必不可少的。但是，建立有效的分离方法来分离分化细胞并排除导致畸胎瘤形成的细胞是将干细胞生物学进步转化为组织替代疗法的主要挑战。传统的分离技术，例如显微镜辅助手动分离是耗时的，而荧光激活的细胞分选和磁激活的细胞分选需要密集的劳动，外源性标记或遗传修饰，因此，不容易适应临床应用。因此，为了解决这些问题，与加利福尼亚大学尔湾分校的传记台系统团队一起发展了高吞吐量电生理纯化阵列（HEPA）系统，用于根据对电刺激的反应的诱导多能干细胞及其分化后代的无标记细胞分选。这阶段的努力将为衍生患者特定细胞的潜在临床用途提供基础用于治疗应用的多个细胞表型。为了证明所提出的平台的可行性，我们将在具有高速信号处理和高吞吐量细胞分类的电极阵列中结合基于流动的场电势传感的技术，以快速检测，识别和排序数百万个特定细胞，以成功地翻译干细胞生物学的进步进入心脏疾病的疗法。